Beast Busters: Second Nightmare is a 3D light gun game co-developed by SNK and ADK for Hyper Neo Geo 64 system. It is the sequel to Beast Busters.

In 2009 A.D, in the International Specialized Pathologies Hospital (ISPH) in a corner of "New Tokyo Port Town", a floating city above Tokyo Bay, an unknown virus breaks out, causing the staff and the patients to mutate into horrific monsters, before spreading to the populace, along with the local animal life. As a result, all contact with the outside world was cut off, and the ISPH became a "Hospital of Death". The United Nations, closely monitoring the situation, deploys two marine commandos to investigate.